Patient-Oriented Evidence That Matters

No Reduction in Delirium with the Use of Haloperidol or Ziprasidone in Critically Ill Patients


Am Fam Physician. 2019 Apr 1;99(7):460-461.

Clinical Question

Does the use of antipsychotics decrease the duration of delirium in critically ill patients with respiratory failure or shock?

Bottom Line

For patients with acute respiratory failure or shock who develop delirium in the intensive care unit (ICU), the use of haloperidol or ziprasidone (Geodon) does not reduce the duration of delirium. This trial was powered to detect at least a two-day difference in the duration of delirium, so a smaller difference cannot be excluded. (Level of Evidence = 1b)


This study included critically ill patients with delirium who were using invasive or noninvasive mechanical ventilation, taking vasopressors, or requiring an intra-aortic balloon pump. The patients were randomized to receive intravenous haloperidol, 2.5 mg; ziprasidone, 5 mg; or a placebo, 0.5 mL of normal saline. Patients 70 years or older received one-half of these doses. Doses were administered every 12 hours and were doubled up to the maximum dose if a patient still had delirium, halved to a minimum dose if the patient did not have delirium for two consecutive assessments, and withheld if a patient did not have delirium for four consecutive assessments. Therapy was continued for 14 days or until ICU discharge. Therapy was stopped permanently if a patient developed torsades de pointes, neuroleptic malignant syndrome, or a severe drug reaction. Of the 20,000 patients screened for eligibility over a six-year period, 566 patients agreed to participate and met the criteria for randomization. Patients in the three groups had similar baseline characteristics, and almost 90% had hypoactive delirium at the time of randomization. Analysis was by intention to treat. Compared with placebo, the use of either haloperidol or ziprasidone did not significantly increase the median number of days alive without delirium or coma (8.5 days with placebo, 7.9 days with haloperidol, 8.7 days with ziprasidone; P = 0.26 for overall effect across all three groups). Additionally, there were no differences in 30-day or 90-day survival, ICU discharge or readmission, or hospital discharge. Excessive sedation was the most common safety end point and did not differ among the groups.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Reference: Girard TD, Exline MC, Carson SS, et al.; MIND-USA Investigators. Haloperidol and ziprasidone for treatment of delirium in critical illness. N Engl J Med. 2018;379(26):2506–2516.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see https://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Editor-in-Chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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